Currently little translational genomic research exists to guide the availability, comprehension, and appropriate uptake of personalized genomics in diverse, general population subgroups that stand to benefit from it in the coming years. The Multiplex Study led by the National Human Genome Research Institute (NHGRI) developed an Internet offer of genomic testing and risk feedback for common diseases, including the melanocortin receptor gene (MC1R) for melanoma risk, that was highly comprehensible, accurately interpreted, and did not increase distress in a primary care population. Melanoma skin cancers are preventable, curable, common in the general population, and disproportionately increasing in Hispanics. Higher risk variants in MC1R are present in about 50% of the population, interact with sun exposure, and confer 2-3 fold melanoma risk in the general population - even darker skin populations - thus feedback regarding MC1R risk status is a potential vehicle to raise risk awareness and protective behavior in the general population. We propose a randomized controlled trial examining Internet presentation of the risks and benefits of personalized genomic testing for melanoma (PGT-M) via MC1R testing (N=885, randomized 6:1 PGT-M versus waiting list control offered testing after outcome assessments, balanced across Hispanic versus Non-Hispanic ethnicity, n=750 in PGT-M arm; n=135 in control arm) comparing personal utility and reach in a general population cohort in Albuquerque New Mexico, where there is year-round sun exposure. Aim I will examine the personal utility of PGT-M in terms of short-term (three month) sun protection, skin screening (i.e., behaviors), communication, melanoma threat and control beliefs (i.e., putative mediators of behavior change). We hypothesize that behaviors and putative mediators will be higher in those who test compared to those who decline testing. Aim 1a will examine potential unintended consequences of testing among those who receive average risk PGT-M findings, examining predictors of sun protection at three months as the outcome. These findings will be used to develop messages for groups that receive average risk feedback. Aim II will compare rates of reach of PGT-M in Hispanic versus Non-Hispanics in terms of consideration of the pros and cons of testing and registration of PGT-M decision. We hypothesize that Hispanics will show reduced reach, but that levels of health literacy, health system distrust, and sociocultural factors (cancer fatalism, family health orientation, skin cancer misconceptions) will explain differences in reach between Hispanics and Non- Hispanics, and provide guidance for future PGT-M modifications for Hispanics. Aim III will examine PGT-M feedback comprehension, recall, satisfaction, and cancer-related distress in those who undergo testing, and whether these outcomes differ by ethnicity (Hispanic versus Non-Hispanic) or sociocultural or demographic factors. The current study will be the first to use the established Multiplex invitation for skin cancer genetic risk testing to examine behavioral outcomes, and the first to use Multiplex to engage a Hispanic population - neither was addressed in the original Multiplex Study. The study will have important implications for personalized genomics in the melanoma context, and will be broadly applicable as a model for delivery of personalized genomic feedback for other conditions, as well. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page